A 70-year-old man, a known case of diabetes mellitus since 10 years ago, presented with lower limb swelling and dyspnea on exertion for one month and dysphagia to solids associated with early satiety for 2 weeks. The patient had palmoplantar keratosis (PPK), which was present since birth with a similar family history. The patient was admitted to rule out esophageal malignancy. Upper gastrointestinal gastroscopy revealed esophagitis and esophageal melanosis with gastric mucosal erythema. Biopsies samples were taken. Histopathological examination revealed reflux esophagitis and chronic active Helicobacter pylori gastritis with no evidence of malignancy. His symptoms improved following H. pylori eradication and treatment for coronary artery disease and heart failure. The patient was advised of regular follow-up as he had risk factors for the development of esophageal melanoma or squamous cell carcinoma.

RASopathies are rare genetic disorders caused by germline pathogenic variants in genes belonging to the RAS/MAPK pathway, which signals cell proliferation, differentiation, survival and death. The dysfunction of such signaling pathway causes syndromes with overlapping clinical manifestations. Skin and adnexal lesions are the cardinal clinical signs of RASopathies, such as cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, formerly known as LEOPARD syndrome, Costello syndrome, neurofibromatosis (NF1), Legius syndrome, Noonan-like syndrome with loose anagen hair (NSLH) and Noonan syndrome. As NF1, one of the most common RASopathies, described in 1882, has its clinical features well delineated, we will focus on the dermatological diagnosis, management and care of non-NF1 RASopathies, which are less known and more recently described. Dermatological manifestations are important clinical diagnostic elements that can aid differential diagnosis among RASopathies. They can affect dermis and epidermis, causing pigmented lesions (melanocytic nevi, café-au-lait spots, and lentigines), hyperkeratosis (keratosis pilaris, ulerythema ophryogenes, and palmoplantar keratosis) or hyperplasia. To date there are rare known links to malignancy, but oftentimes skin lesions require close attention because they can highly affect quality of life.

Pathogenic sequence changes in mitochondrial DNA (mtDNA) are one of the most common causes of genetic hearing loss. We report an infant with palmoplantar hyperkeratosis, extrapalmoplantar cutaneous features and mitochondrial sensorineural hearing loss caused by the previously reported pathogenic NC_012920:m.7445A > G sequence change in the mitochondrial gene COX1 (COX1, MT-CO1). Next generation sequencing- based technology was key for the diagnosis and management of this patient.

Keratitis-ichthyosis-deafness syndrome is a rare genetic disease presenting with cutaneous, ocular, and otic defects. This comprehensive review provides insight into the clinical presentations, highlighting the cutaneous manifestations including histopathology and treatment options.

BACKGROUND: Papillon Lefevre syndrome (PLS) is an autosomal recessive disorder that results from a mutated gene that encodes a lysosomal peptidase known as cathepsin C (CTSC). The clinical presentation of PLS involves mainly palmoplantar keratosis and periodontitis with a variable degree of severity.
METHODS: and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting.
RESULTS: Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients\' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins.
CONCLUSIONS: Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis.

Nagashima-type palmoplantar keratosis (NPPK) is a diffuse, non-syndromic (isolated), autosomal recessive palmoplantar keratoderma (PPK) with transgredients. It is characterized by non-progressive mild to moderate transgredient PPK. The mutation in SERPINB7 is reported to underlie the condition. Though many case reports/series have demonstrated various mutations in SERPINB7, the genotype-phenotype correlation in this disorder is still lacking. We herein report two brothers with NPPK. Both patients were found to be compound heterozygous for c.796C>T and c.650_653delCTGT in the SERPINB7 gene. We then summarize the previously reported cases of different mutations in SERPINB7 along with their clinical phenotypes in an attempt to shed some light on this correlation. Further investigations and systematic data collection are still needed to clarify this issue.

Papillon-Lefèvre syndrome (PLS) is a rare genetic disorder characterized by palmoplantar keratosis and premature loss of primary and permanent dentition. Its onset can be as early as 1-4 years of age. The genetic disorder is mutation in the cathepsin C gene. Hereby, we discuss the fabrication of Cu-sil dentures for the prosthetic rehabilitation of a 14-year-old girl with PLS. The case report describes the procedure and associated relevant information regarding the management protocols.

BACKGROUND: Mutations in the desmoplakin (DSP) gene have been demonstrated to be associated with lethal acantholytic epidermolysis bullosa, cardiomyopathy, and palmoplantar keratoderma (PPK).
OBJECTIVE: To better understand the relationship between PPK and the gene mutations in DSP.
METHODS: A pedigree of PPK was subjected to heterozygous missense mutation analysis in the DSP gene. Dermoscopy, reflectance confocal microscopy, and histopathological examination were performed from each epidermis layer in this study. Samples were derived from the blood of patients and normal healthy controls. DSP gene sequence analysis and Q-PCR analysis was performed for evaluating DSP gene mutation and expression.
RESULTS: A novel heterozygous missense mutation c.3550 C>T in the coding region of the DSP gene, predicting substitution of arginine (Arg,R) by tryptophan (Trp,W) in the desmoplakin polypeptide, was discovered in a Chinese pedigree of PPK. In the meanwhile, this mutation was not found in 100 healthy individuals.
CONCLUSIONS: The novel missense mutation c.3550 C>T(p.Arg1184Trp) of DSP gene expanded the mutation spectrum in palmoplantar keratoderma.

Premature tooth loss is a disastrous situation that affects deciduous or permanent teeth era with different causes. It may be attributed to some disorders like Papillon-Lefevre syndrome or coffin-lowry syndrome but because of ambiguous nature, precise diagnosis is not easily possible. Moreover, it has very low incidence and defines by few and limited case series, with vague characters to some extent, confusion in detecting the right diagnosis is a common possibility. Hence, it is expectable to have a wrong diagnosis for this case. In this study, a 5-yr-old boy with chief complaint of early tooth loss despite having blindness in left eye and palmar keratosis is reported, although he had some other manifestation of oculodentodigital dysplasia (ODDD) like ataxia, dysarthria and nail deformity, ignoring other extra and intra oral finding. He was diagnosed as Papillon-Lefevre syndrome already, just because of early tooth loss and palmar keratosis.

BACKGROUND: Papillon-Lefèvre syndrome is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressively progressing periodontitis leading to premature loss of deciduous and permanent dentition. The etiopathogenesis of the syndrome is relatively obscure, and immunologic, genetic, or possible bacterial etiologies have been proposed.
METHODS: A series of five cases of Papillon-Lefèvre syndrome among the siblings in a family is presented here: a 3-year-old Arab girl, a 4-year-old Arab boy, a 11-year-old Arab boy, a 12-year-old Arab boy, and a 14-year-old Arab boy. The patients presented with severe gingival inflammation and mobility of teeth. The clinical manifestations were typical of Papillon-Lefèvre syndrome and the degree of involvement of the oral and skin conditions varied among them.
CONCLUSIONS: This case series stresses the consanguinity in the family as an etiologic factor. All siblings in the family were affected with Papillon-Lefèvre syndrome which makes this a rare case. A multidisciplinary approach with the active participation of a dental surgeon, dermatologist, and pediatrician is essential for the management of cases of Papillon-Lefèvre syndrome.